IL27RA encodes the interleukin-27 receptor alpha subunit, a transmembrane receptor located on the cell surface that mediates IL-27 signaling through association with IL6ST/GP130 1. The receptor activates STAT1 and STAT3 phosphorylation 2, triggering downstream signaling cascades including p38 MAPK and PI3K/AKT pathways 34. IL27RA functions in metabolic regulation and immune homeostasis. IL-27-IL27RA signaling promotes brown adipocyte thermogenesis via p38 MAPK-PGC-1α activation and UCP1 production, protecting against diet-induced obesity and insulin resistance 3. The receptor suppresses pathogenic type 17 immune responses by inhibiting IL-17 production from γδ T cells through metabolic reprogramming 5, and restrains innate cytotoxic lymphocyte activity in hepatocellular carcinoma, serving as an immunologic checkpoint 6. IL27RA is critical for antiviral immunity. IL27RA deficiency impairs CD8+ T cell expansion against Epstein-Barr virus, increasing severe infectious mononucleosis risk 2. Conversely, IL-27-IL27RA signaling restricts Zika virus infection at the maternal-fetal interface by upregulating antiviral genes 7. The receptor also supports reproductive function, promoting endometrial decidualization through STAT3-mediated estrogen and progesterone receptor upregulation 8. Clinically, IL27RA upregulation in triple-negative breast cancer drives immunotherapy resistance by suppressing MHC-I expression 4, while elevated serum IL-27 associates with obesity resolution 3.